Medical Specialties Commons^™

Room To Wiggle, Holden Caplan, Bs

inSIGHT

Uveitis – inflammation of the inside of the eye and the fifth leading cause of vision loss in the USA. Uveitis (of which there are 30-40 types) may be infectious or non-infectious, unilateral or bilateral, of sudden onset or progressing over months to years, and present in any age group. Different etiologies cause different presentations, including both onset and location (front, middle, or back; Table 1) in the eye.

Exploring The Debate: Dmek And Dsek In Corneal Transplantation, Christian Raimondo, Bs

inSIGHT

Scientific progress is rarely a linear process. This notion is especially true as it pertains to the development of surgical techniques that have the potential to shape future clinical landscapes. Corneal transplantation is no exception. From the very first iterations of full corneal transplants performed in the 19th century to the highly nuanced endothelial procedures available today, corneal medicine has served — and continues to foster — an academic arena where research discoveries and surgical innovations come together to advance the field.

Review Of Surgical Management For Closed-Angle Glaucoma, Scott Kozarsky, Ba

inSIGHT

Closed-angle glaucoma, also known as angle-closure glaucoma, is one of the major types of glaucoma. Glaucoma is a term used to describe a broad group of ocular diseases that damage the optic nerve. The type of angle closure with which the patient presents, whether acute, subacute, or chronic, will dictate their treatment. Management of these three presentations will be discussed at length later in this article. In the United States, closed-angle glaucoma is less common than open-angle glaucoma, which often has a gradual onset of intraocular pressure (IOP) elevation and optic nerve damage.

Age-Related Macular Degeneration And Emerging Treatments – With Advice From Dr. Ajay Kuriyan On Balancing Research With Clinical Responsibilities, Charles Deyoung, Ba

inSIGHT

Age-related macular degeneration (AMD) is a chronic disease of the central retina and a leading cause of vision loss worldwide. Although the early stages of AMD may present asymptomatically, the disease may progress and lead to severe visual impairment via geographic atrophy (“late dry”) or neovascular (“wet”) AMD. In geographic atrophy (GA), there is progressive atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and photoreceptors due to lipofuscin (Drusen) accumulation between the RPE and Bruch’s membrane.¹ These Drusen deposits grow and create an inflammatory and metabolically dysfunctional environment for the photoreceptors supplying the macula (Figure 1).² Eventually, the …

Insight, Volume 3, Issue 1, 2023

inSIGHT

Contents

8 - Age-Related Macular Degeneration and Emerging Treatments
By Charles F. DeYoung

13 - Review of Surgical Management for Closed-Angle Glaucoma
By Scott C. Kozarsky

18 - Exploring the Debate: DMEK and DSEK in Corneal Transplantation
By Christian Raimondo

23 - Room to Wiggle
By Holden Caplan

30 - Ophthalminute Highlight
By Anza Rizvi

34 - Thyroid Eye Disease: Overview and Treatment
By Michelle Omega

38 - Current Barriers to Eye Care
By Annika G. Samuelson

Seeing Eye To Eye: An Overview Of Strabismus And Approach To Treatment, Shreya Swaminathan, Bs

inSIGHT

Strabismus is a heterogenous group of conditions characterized by the misalignment of the eyes. It may manifest as constant or intermittent deviation, meaning the eyes sometimes appear well aligned, or straight, and sometimes appear misaligned. Vision can be normal in some patients, but when associated with amblyopia, may be decreased vision in one eye. There is sometimes diminished binocular vision, with decreased depth perception.

A Look Into Oculoplastics: Repairing Lower Eyelid Defects From Carcinomas, Cameron Haghshenas, Bs

inSIGHT

Eyelids are the thinnest, most sensitive skin we have and can easily be damaged by sun exposure. This is evident given that 5 - 10% of all skin cancers occur on the eyelid, and over half of these occur on the lower eyelid¹. Most of such cases are basal cell carcinomas, which are slow-growing cancers that arise from the basal cell layer, the deepest part of the epidermis. If left untreated or improperly treated, these tumors can extend into adjacent tissues and bone, or recur. Squamous cell carcinomas can also occur on the lower eyelid, although they represent …

Manual Small-Incision Cataract Surgery, Ankur Nahar, Bs

inSIGHT

Of the 49 million people living with blindness worldwide, 15.2 million are blind due to cataracts, making it the leading cause of preventable blindness.^1,2 Furthermore, 65.2 million people experience moderate to severe vision impairment from cataracts, according to the World Report on Vision published by the World Health Organization (WHO).³ While global cataract surgery efforts have been a major success over the past three decades, an aging population has resulted in a rapid rise in cataracts, primarily in low- and middle-income countries (LMICs).^2,4 To address the increasing demand for cataract treatment, countries must perform an equal or …

Gatt: A Micro-Invasive Glaucoma Surgery And A Big Step For Glaucoma Treatment, Mose Im, Bs

inSIGHT

Glaucoma is a group of ocular diseases characterized by damage to the optic nerve that may lead to permanent vision loss. Currently, 76 million people (aged 40-80 years) suffer from glaucoma, and the prevalence is projected to increase to 111.8 million by 2040.¹ The diagnosis of glaucoma can be frightening, particularly because there is no known cure. Fortunately, recent advancements in glaucoma surgery have made more options available for patients presenting with new-onset glaucoma. In particular, patients with mild to moderate glaucoma may be eligible for newer minimally invasive glaucoma surgeries (MIGS). This review is both an overview of …

Origins Of The Wills Eye Manual: Surviving The Test Of Time, Jordan Safran, Bs

inSIGHT

The first copy of the Wills Eye Manual hit the press in late 1989; it featured a black cover page with bold gold lettering and the Wills Eye logo proudly displayed on top. Published in a time before the invention of the world wide web or the advent of digital printing, this 450-page expertly sourced ocular disease reference guide took the ophthalmology world by storm. Since its debut, the manual has served as the go-to guide for trainees and seasoned physicians alike in diagnosing and treating more than 200 ocular diseases. To date, the Wills Eye Manual has published eight …

A Day In The Life In The Wills Er, Samara Hamou, Ms1

inSIGHT

The Wills Eye Hospital — among the greatest eye hospitals in the country — is a force to be reckoned with. Located in Center City Philadelphia, the eight-story tall brick facility will capture your attention as you stroll down Walnut Street. The entrance to the Wills Eye Emergency Room (ER), however, is less apparent to the average city-goer. Located directly across from the Hospital, the red and blue entrance sign may go unnoticed to the unsuspecting by passer. However, for those who require expert eye care in a timely fashion, the Eye Emergency Room is a signal for the invaluable …

Neuro-Ophthalmology Subspecialty Highlight: With Dr. Sarah Thornton, Wills Eye Hospital, Joseph D. Desimone, Bs

inSIGHT

Neuro-Ophthalmology is a subspecialty within ophthalmology that combines the complexities of nervous system disease with the intricacies of the ocular manifestations of those diseases. Neuro-ophthalmologists work closely with neurologists, neurosurgeons, rheumatologists, and other ophthalmologists in different subspecialties, such as retina and glaucoma, to get to the source of their patients’ problems. Neuro-ophthalmology is typically a 1-year fellowship undertaken after residency training is completed, where physicians will learn the complex ways different diseases can manifest in the eye.

A New Dimension To Offer, Ari August, Bs

inSIGHT

Technological advancements are crafted, fielded, and sold from the vantage point of benefit: How can this make my life better? The origins of three-dimensional (3D) technology are no different. 3D technology targets the mind’s ability to make sense of two different angles of an image, and therefore perceive depth. Earlier models, common in movie theaters and cereal box toys, utilized red and blue lenses to outwit one’s perception of a flat image and project it into 3D images, promising deeper immersive experiences and even “x-ray vision.” More recently, the capacity of 3D technology has expanded, as seen with the recent …

Longitudinal Variations In Antibody Responses Against Sars-Cov-2 Spike Epitopes Upon Serial Vaccinations, Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood

LSU-LCMC Cancer Center Faculty Publications

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen …

Covid-19 Related Biliary Injury: A Review Of Recent Literature, Sujani Yadlapati, Simone A. Jarrett, Daniel Baik, Adib Chaaya

COVID-19 Papers, Posters, and Presentations

Since its emergence in 2019, it has become apparent that coronavirus 2019 (COVID-19) infection can result in multi systemic involvement. In addition to pulmonary symptoms, hepatobiliary involvement has been widely reported. Extent of hepatic involvement ranges from minor elevation in liver function tests (LFTs) to significant hepatocellular or cholestatic injury. In majority of cases, resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection. However, severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation. Due to the timing of its presentation, …

Mechanisms Of Chromosomal Instability (Cin) Tolerance In Aggressive Tumors: Surviving The Genomic Chaos, Brittiny Dhital, Veronica Rodriguez-Bravo

Student Papers, Posters & Projects

Chromosomal instability (CIN) is a pervasive feature of human cancers involved in tumor initiation and progression and which is found elevated in metastatic stages. CIN can provide survival and adaptation advantages to human cancers. However, too much of a good thing may come at a high cost for tumor cells as excessive degree of CIN-induced chromosomal aberrations can be detrimental for cancer cell survival and proliferation. Thus, aggressive tumors adapt to cope with ongoing CIN and most likely develop unique susceptibilities that can be their Achilles' heel. Determining the differences between the tumor-promoting and tumor-suppressing effects of CIN at the …

Longitudinal Variations In Antibody Responses Against Sars-Cov-2 Spike Epitopes Upon Serial Vaccinations, Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood

School of Medicine Faculty Publications

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen …

Met Alterations Are Associated With Osimertinib Resistance In Egfr Mutant Lung Cancers, A Meta-Analysis, Annie Le, Marissa Viola, Jun Wang

Research Day

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has been used to treat EGFR mutant lung cancers, especially those with EGFR T790M mutation. Resistance to osimertinib is likely associated with acquired genetic alterations in these cancer cells. Mesenchymal epithelial transition (MET) is a tyrosine kinase and its amplification is frequently seen in osimertinib resistant patients. To investigate whether the presence of MET alteration is associated with osimertinib resistance, a meta-analysis was conducted using published observations of EGFR mutant lung cancer patients treated with osimertinib. Frequencies of MET alterations are variable, ranging from 0-43% in osimertinib resistant patients. MET alteration …

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

Occupational Therapy In End-Of-Life Care, Shannon Sudrla

Student Capstone Papers

Patients at the end-of-life (EoL) experience functional decline in response to terminal illness and the active dying process, inhibiting participation and engagement in meaningful daily activities. Occupational therapy practitioners (OTP) are equipped to address patients’ occupational needs and desires despite their declining capacities; however, the absence of occupational therapy (OT) services in EoL care leaves patients’ occupational needs unmet, directly affecting their quality of life. The literature demonstrates the need for enhanced education and training among occupational therapy students (OTS) and practitioners to better prepare them to work with terminally ill patients who face progressive functional decline and imminent death. …

Phase Ii Study Of Palbociclib (Pd-0332991) In Ccnd1, 2, Or 3 Amplification: Results From The Nci-Match Ecog-Acrin Trial (Eay131) Subprotocol Z1b, Amy S Clark, Fangxin Hong, Richard S Finn, Angela M Demichele, Edith P. Mitchell, James Zwiebel, Fernanda I Arnaldez, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David Patton, P Mickey Williams, Stanley R Hamilton, Mehmet S Copur, Samer S Kasbari, Ravneet Thind, Barbara A Conley, Carlos L Arteaga, Peter J O'Dwyer, Lyndsay N Harris, Alice P Chen, Keith T Flaherty

Department of Medical Oncology Faculty Papers

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.

Patients and methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

Bayesian Adaptive Model Selection Design For Optimal Biological Dose Finding In Phase I/Ii Clinical Trials, Ruitao Lin, Guosheng Yin, Haolun Shi

Faculty, Staff and Student Publications

Identification of the optimal dose presents a major challenge in drug development with molecularly targeted agents, immunotherapy, as well as chimeric antigen receptor T-cell treatments. By casting dose finding as a Bayesian model selection problem, we propose an adaptive design by simultaneously incorporating the toxicity and efficacy outcomes to select the optimal biological dose (OBD) in phase I/II clinical trials. Without imposing any parametric assumption or shape constraint on the underlying dose-response curves, we specify curve-free models for both the toxicity and efficacy endpoints to determine the OBD. By integrating the observed data across all dose levels, the proposed design …

The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for …

Feature Selection For Support Vector Regression Using A Genetic Algorithm, Shannon B Mckearnan, David M Vock, G Elisabeta Marai, Guadalupe Canahuate, Clifton D Fuller, Julian Wolfson

Faculty, Staff and Student Publications

Support vector regression (SVR) is particularly beneficial when the outcome and predictors are nonlinearly related. However, when many covariates are available, the method's flexibility can lead to overfitting and an overall loss in predictive accuracy. To overcome this drawback, we develop a feature selection method for SVR based on a genetic algorithm that iteratively searches across potential subsets of covariates to find those that yield the best performance according to a user-defined fitness function. We evaluate the performance of our feature selection method for SVR, comparing it to alternate methods including LASSO and random forest, in a simulation study. We …

Mmp9 Clears The Way For Metastatic Cell Penetration Across The Blood-Brain Barrier, Joseph H Mccarty

Faculty, Staff and Student Publications

Although brain metastases are 10-fold more prevalent than primary brain cancers, relatively little is understood about the genes and pathways that promote metastatic cell entry, growth, and survival in the brain. Hence, determining how metastatic tumors colonize the brain and thrive within the neural microenvironment is a topic of both fundamental importance and direct clinical relevance. In this issue, a report by Karreman and colleagues explores pathways that are exploited by metastatic tumor cells to arrest in the circulation, cross the endothelial blood-brain barrier (BBB), and thrive in the brain microenvironment. The authors used elegant imaging tools including intravital fluorescence …

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …